301155-96-4Relevant academic research and scientific papers
Multi-Functional Oxidase Activity of CYP102A1 (P450BM3) in the Oxidation of Quinolines and Tetrahydroquinolines
Li, Yushu,Wong, Luet L.
, p. 9551 - 9555 (2019/08/06)
Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48-variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation-selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4-dihydro-2-quinolinones at most positions around the two rings in good to high yields at synthetically relevant scales (1.5 g L?1 day?1). Other oxidase activities, such as C?C bond desaturation, aromatization, and C?C bond formation, were also observed. The enzyme variants, with mutations at the key active site residues S72, A82, F87, I263, E267, A328, and A330, provide direct and sustainable routes to oxy-functionalized derivatives of these building block molecules for synthesis and drug discovery.
Preparation of optically enriched 3-hydroxy-3,4-dihydroquinolin-2(1H)-ones by heterogeneous catalytic cascade reaction over supported platinum catalyst
Szollosi, Gyoergy,Makra, Zsolt,Kovacs, Lenke,Fueloep, Ferenc,Bartok, Mihaly
, p. 1623 - 1629 (2013/07/04)
The development of a novel heterogeneous catalytic asymmetric cascade reaction for the synthesis of tetrahydroquinolines from 2-nitrophenylpyruvates is reported. Optically enriched 3-hydroxy-3,4-dihydroquinolin-2(1H)-ones are prepared by enantioselective hydrogenation of the activated keto group over a Cinchona alkaloid-modified Pt catalyst, reduction of the nitro group and spontaneous cyclization cascade. Acceleration of the enantioselective hydrogenation of the activated keto group over the catalyst modified by Cinchona alkaloids ensured high tetrahydroquinolinone selectivities. The scope of the reaction was checked using twelve substrates. Both yields and enantioselectivities were significantly influenced by the nature and position of the substituents on the phenyl ring. Substituents adjacent to the nitro group considerably increased the product yield, due to their effect on the nitro group′s reduction rate; however, had only a limited effect on enantioselectivities. Copyright
Unexpected formation of quinolone derivatives in Reissert indole synthesis
Suzuki,Gyoutoku,Yokoo,Shinba,Sato,Yamada,Murakami
, p. 1196 - 1198 (2007/10/03)
The Reissert indole synthesis was found to unexpectedly give 3-hydroxy-1,2,3,4-tetrahydro-2-quinolone derivative 4, sometimes in a high ratio with the expected ethyl indole-2-carboxylate derivatives 3 in a low ratio, depending on the conditions of the catalytic reduction of the intermediate 2-nitrophenylpyruvate 2. This reactivity is characteristic in the preparation of 7-substituted indoles.
